tbuckley/cabot-search huggingface dataset:
20-year incidence trends of anal squamous cell carcinoma.
Authors: Khushali Jhaveri, Karnav Modi, Humaira Sarfraz, Aditi Saha, Melanie Buhlmann, Michael J. Schell, Richard D. Kim
Journal: Journal of Clinical Oncology (2023)

e15503 Background: Anal Squamous Cell Carcinoma (SCCA) accounts for 90% of cases of anal cancer. ~95% of SCCAs are driven by Human Papilloma Virus (HPV). We did a follow-up population-based analysis to assess incidence trends of SCCA over 20 years (2000-2019) in era of HPV vaccination (available since 2006). Methods: Data was extracted from Surveillance, Epidemiology, and End Results (SEER) database for years 2000-2019. Joinpoint regression models were fitted to identify a discrete joints (year) that represented a statistically significant change in direction of the trend of overall SCCA incidence. The average annual percentage change (AAPC) in age-adjusted incidence rate in all subgroups pre- and post-2009 (statistically significant joinpoint year) was measured. (Table 1). Results: 30,294 new cases of SCCA were identified from 2000-2019, with majority in females (61.6%), white population (86.5%), and ages 40-79 years (84.1%). A significant joinpoint for SCCA incidence was observed in 2009, wherein APC of 2.8% (95% CI 2.0-3.6) in 2000-2009 was reduced to 0.5% (95% CI -0.1-1.2) in 2009-2019 (82% relative reduction [RR]). In subgroup analysis, evaluating the trends after identifying a discrete joint (2009), we found that APC for White population reduced from 3.1% (P &lt; 0.0001) to 1.1% (P = 0.022) (65% RR), and for Black population, APC of 3.2% (P = 0.0015) seem to flatten out at 0.3% (P = 0.768) in post-2009 years (91% RR). Ages 20-39 had a -4.2% (P = 0.028) APC pre-2009 that showed increase to 1.3% (P = 0.214) post-2009, however, small sample size noted. In ages 40-59, APC of 4.7% (P &lt; 0.0001) seem to flatten out at -0.5% (P = 0.393) (111% RR). Ages 60-79 had a similar APC (2.4% [P = 0.0011] and 2.5% [P = 0.0001], respectively). In males, APC of 2.8% (P = 0.002) flattened out to 0.5% (P = 0.249) and females reduced from 3.2% (P &lt; 0.001) to 1.2% (P = 0.009). Conclusions: In this study, we found a trend of decrease in the rate of growth of SCCA incidence pre- and post-2009, overall and among various subgroups. Furthermore, our results suggest that widespread education and scaling up access to HPV vaccination can decrease and potentially reverse the SCCA incidence. [Table: see text]
HER2 in situ hybridization testing in breast cancer: Applying algorithm-assisted assessment to reduce interobserver variability in difficult cases.
Authors: Madeline Gough, Cheng Liu, Bhuvana Srinivasan, Lisa Wilkinson, Louisa Dunk, Yuanhao Yang, Haitham Tuffaha, Thomas Kryza, John D. Hooper, Sunil R. Lakhani, Cameron Edward Snell
Journal: Journal of Clinical Oncology (2023)

e13561 Background: Accurate assessment of HER2 expression by HER2 immunohistochemistry and in-situ hybridization (ISH) is critical for the management of patients with breast cancer. The revised 2018 ASCO/CAP guidelines defined 5 subgroups based on HER2 expression and copy number. Few reports have investigated interobserver variability when applying the revised guidelines. Digital algorithms may have a role in assisting pathologists in assessing cases with equivocal and uncommon patterns of HER2 amplification. This study was designed to evaluate interobserver variability in the gold standard manual assessment of HER2 ISH, particularly in less common HER2 ISH groups. Subsequently, we evaluated whether a new digital image analysis algorithm (Roche uPath HER2 Dual ISH image analysis) could reduce interobserver variability and potentially improve patient selection for targeted anti-HER2 therapy. Methods: Of 2982 breast cancer cases, we derived an enriched cohort of 99 patient cases with HER2 IHC 2+ or 3+ and selective ISH results (groups 2-4, evidence of HER2 heterogeneity, borderline negative group 5 and borderline positive group 1). As per guidelines, a minimum of 20 tumour cells per slide were manually and independently counted by 4 anatomical pathologists. After a washout period and second round of de-identification, the slides were scanned (DP200; Roche) and re-scored using the digital algorithm. Results: Pathologist reporting of patient HER2 status (HER2 positive vs. HER2 negative) using manual microscopy demonstrated significant interobserver variability, with a Fleiss’s kappa value of 0.471 (95% CI: 0.378-0.564; P= 1.24E-21) indicating fair-moderate agreement. Interobserver variability in manual scoring of HER2 ISH at the level of HER2 group designation (groups 1-5) showed poor-moderate reliability between pathologists, with an intraclass correlation coefficient (ICC) of 0.526 (95% CI: 0.407-0.641; P= 9.28E-21). Repeat analysis of the cohort using algorithm-assisted quantification resulted in moderate-substantial concordance in HER2 patient status reporting, with a Fleiss’s kappa value of 0.666 (95% CI: 0.572-0.759; P= 1.70E-40). Algorithm-assisted quantification resulted in moderate-good agreement of HER2 group designation, with an ICC of 0.763 (95% CI: 0.683-0.832; P= 8.76E-48). In sub-group analysis, use of the algorithm improved concordance particularly in groups 2,4 and 5. Time to report cases was also significantly reduced with the use of the algorithm. Conclusions: Our study demonstrates the potential to improve the concordance of HER2 amplification status reporting in less common HER2 subgroups using a digital algorithm and potentially improve therapy selection and outcomes for patients with HER2-low and borderline HER2-amplified breast cancers.
Surgically targeted radiation therapy (STaRT) for recurrent glioblastoma: Initial outcomes from a prospective multicenter registry.
Authors: Ahmad Ozair, David Brachman, Lisa Campbell, Clark C Chen, Toral R. Patel, John Floyd, Devon H Hayden, Adam W Nowlan, Andrea C Wasilewski, John Wanebo, Mitesh Shah, Angela Richardson, Simon Hanft, Ondrej Choutka, Colette Shen, Zabi Wardak, Stuart Lee, Tulika Ranjan, Atulya Aman Khosla, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2023)

2038 Background: Surgically targeted radiation therapy (STaRT), using a novel bioresorbable collagen brachytherapy device containing 4 Cesium-131 sources, is FDA-cleared for use as adjuvant radiation therapy (RT) post-resection in both newly diagnosed and recurrent intracranial neoplasms. Intraoperative initiation of brachytherapy potentially minimizes post-resection tumor regrowth with a favorable dosimetric profile compared to external beam radiation. This work sought to determine early patterns of care and the safety of this approach in recurrent GBM. Methods: This prospective multi-institutional observational study (NCT04427384) included recurrent GBM patients who underwent maximum safe resection (MSR) and permanent implantation of the device(s) (GammaTile, GT Medical Technologies, Tempe, AZ, US). Descriptive and comparative analyses regarding patient characteristics and early clinical outcomes were performed. Toxicities were categorized using the CTCAE v5.0 adverse event (AE) criteria. Results: During 10/2020–01/2023, 14 participating sites enrolled 45 patients with recurrent GBM for STaRT; 2 patients had two sites treated for a total of 47 implants. 67% of patients were treated at the first recurrence, 24% at the second, and 13% at the third, respectively. The median age was 61 (range 28-75), 36% were female, and 23% were &gt; 65 years. 85% of patients received prior same-site RT with the median time from last RT to implantation of 14.6 months (range 3.5-57). The median maximum preoperative size was 4.2 cm (range 1.6-7.0) and the median volume was 20.8 cm 3 (range 0.8-130). 68% of resections were gross-total, 17% near-total, and 15% sub-total; the median time needed for device implantation was 5 minutes (range 1.0-13). Median follow-up was 5.2 months (range 0.6-23.2). Median Karnofsky performance status (KPS) at screening, at initial postoperative assessment, and 3 months were all 80 (range 40-100). 7 attributed AEs occurred in 13% (6/45) of patients, all grade 3 AEs: 2 CSF leaks, 2 seizures, 1 cerebral edema, 1 pseudomeningocele, and 1 left hemiparesis. All except one were coded as related to both radiation and surgery; the patient with pseudomeningocele experienced a seizure at 47 days that was considered related to radiation alone. Conclusions: Early data from this prospective registry demonstrate the feasibility and safety of STaRT in recurrent GBM. Data on 6-month progression-free survival will be presented at the conference. A prospective randomized trial of adjuvant systemic therapy (AST) +MSR+STaRT versus MSR+AST is planned for initiation in 2023.
Ribosomal protein S26 (RPS26) expression of advanced cervical cancer (CC) to predict response to programmed death-1 inhibitor combination therapy: A secondary analysis of the CIBI308ALTER-C201 trial.
Authors: Jing Liu, Li Li, Ying Chen, Yanwen Song, Lan Luo, Shitao Zhu, Qin Xu
Journal: Journal of Clinical Oncology (2023)

e17520 Background: PD-1 inhibitor combination therapy is widely used in cervical cancer, and improves prognosis. However, there is still a lack of effective predictive markers. The results of previous single-cell analysis of cervical cancer in our research group suggested that RPS26 is related to changes in the immune microenvironment. The purpose of this study is to evaluate whether RPS26 can be used as a prognostic marker for cervical cancer PD-1 inhibitor combination therapy. Methods: A total of 36 patients with CC were recruited. 18 patients were from CIBI308ALTER-C201 trail，and the other 18 were not. All patients underwent next-generation sequencing (NGS). Tumor RPS26 expression was assigned by immunohistochemistry as follows: 0, 1+, 2+, 3+. Significant difference was tested by Fisher's exact test. Kaplan-Meier analysis were applied for survival analysis. Results: The PFS of patients from CIBI308ALTER-C201 trail was significantly longer among patients with RPS26 expression for 2+/3+ than 0/1+ (not reached v 9.877 months, p= 0.0497). There were 11, 14, 9 and 2 patients with RPS26 expression of 0, 1+, 2+, and 3+, respectively. There were 12 and 24 for PIK3CA mutant patients and wild-type, respectively. There was no patient with RPS26 expression for 0 in the PIK3CA mutant group, and 9 patients with RPS26 expression for 0 in the PIK3CA wild group. The expression of RPS26 was significantly different between the two groups ( p= 0.0163). Conclusions: Our study suggested that RPS26 could be novel predictive biomarkers in patients with CC treated with PD-1 inhibitor combination therapy, and PIK3CA mutation enhances RPS26 expression in CC.
A phase 2 trial of chemotherapy, pembrolizumab, and propranolol in patients with advanced esophageal/gastroesophageal junction adenocarcinoma (EGAC).
Authors: Sarbajit Mukherjee, Karan Jatwani, Sarah Chatley, Christos Fountzilas, Sylvia Vania Alarcon Velasco, Deepak Vadehra, Renuka V. Iyer, Kristopher Attwood, Mark Farrugia, Anurag K. Singh, Elizabeth A. Repasky
Journal: Journal of Clinical Oncology (2023)

TPS4171 Background: Chronic stress suppresses the immune system and promotes cancer cell growth. In animal studies, we reported that this is mediated by the beta-adrenergic (BA) pathway. We further showed that concurrently blocking the BA pathway with β-blockers (BB) can improve immune checkpoint inhibitor (ICI) efficacy. Our retrospective data analysis revealed that esophageal cancer (EC) patients taking BB for other non-cancer reasons while receiving chemoradiation had significantly better survival and distant control than those not taking BB. We hypothesized that blocking the effects of adrenergic stress with a commonly used BB, propranolol, will improve response to therapies in EC patients. Methods: This is an open-label, non-randomized, phase 2 study of propranolol combined with pembrolizumab and standard chemotherapy in frontline unresectable/metastatic EGAC. Eligible patients must be treatment-naïve, have adequate organ function, have an ECOG performance status of 0 –1, and be able to swallow and retain oral medication. Patients with Her-2 positive cancer, active autoimmune disease, active HIV, Hepatitis B or C, or a history of non-infectious pneumonitis/interstitial lung disease that requires treatment, are ineligible. Patients who are on BB for various indications are also ineligible. Eligible patients will receive mFOLFOX6 every two weeks in combination with pembrolizumab 400 mg intravenously every six weeks and propranolol 30 mg orally twice daily. The mFOLFOX6 dosing regimen will consist of dl-LV 400 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 5-FU 400 mg/m2 and a 48-hour infusion of 5-FU 2400 mg/m2. The study will include an initial safety lead-in cohort of six patients. The primary endpoint is the overall response rate (ORR) determined by RECIST 1.1. Secondary endpoints include safety, progression-free survival (PFS), overall survival (OS), and ORR as determined by iRECIST. Correlative studies will assess baseline levels or changes in the levels of biomarkers, like, peripheral T-cell subsets/myeloid-derived suppressor cells (MDSC)/cytokines/ and perceived stress scale PSS/chronotropic effects of exercise with efficacy (ORR, PFS, OS). Assuming a historic ORR of 50% with standard treatment, 37 evaluable pts are needed to show a 20% increase in ORR with our proposed treatment with 80% power at a one-sided significance level of α = 0.1. In stage 1, n1= 23 evaluable pts will be enrolled. If there are 13 or more ORRs, an additional n2= 14 pts will be enrolled in stage 2. If 24 or more ORRs are observed in the total n = 37 evaluable pts, the proposed treatment regimen will be considered promising for further study. The study is currently open to enrollment. Clinical trial information: NCT05651594 .
Effect of multi-targeting bacterial gene therapy on tumour regression and survival in mouse models of ovarian and intraperitoneal cancer.
Authors: Haritha Samaranayake, Jere Kurkipuro, Wesley Smith, Igor Mierau, Hanna-Riikka Kärkkäinen, Mirka Tikkanen, Laurent Décory, Thomas Wirth, Juha Yrjänheikki
Journal: Journal of Clinical Oncology (2023)

e17550 Background: With a prevalence of more than 2 million cases, a 5-year survival below 20% in stage 3 and 4, and limited treatment options, ovarian cancer represents a significant unmet medical need. We assessed the efficacy of AUP-55, a genetically engineered Lactococcus cremoris for the treatment of ovarian cancer and peritoneal carcinomatosis. We evaluated the efficacy of two AUP-55 leads producing human therapeutic proteins in situ; namely interleukin 18 (IL-18), granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-12 (IL-12) and interferon alpha (IFN-A) in syngeneic intraperitoneal ID8 ovarian cancer and B16F1 melanoma models in mice. Methods: ID8-Luc-mCherry-Puro ovarian cancer model was used for survival and tumor burden by bioluminescent imaging with post-mortem pathology for all animals, whereas the B16F1 melanoma model was used solely for survival. Animals were treated daily or every other day with i.p injections of the AUP-55 leads (1e8 CFU/dose for 12-22 times). Results: In the ID8 model treatment was started 14 days after tumor implantation. Most untreated mice were terminated due to the disease progress. Treatment with AUP-55 resulted in 91.3 % survival and lower tumor load during the study duration of 81 days compared to the 0 % survival and massively increased tumor load in untreated mice. When compared to the available data from the CRO, the survival advantage was superior to, for example anti-PD1 and cisplatin treatments in the same model. In the B16F1 model, treatment with AUP-55 led to 90 % survival in comparison to 10 % untreated mice. All AUP-55 treatments were well tolerated. In the pathology post-mortem, all untreated animals had typical findings for ovarian cancer, such as ascites and high number of tumor nodules present in abdominal cavity, liver, spleen, kidney and pancreas. In the group treated with AUP-55 there were no macroscopic tumor deposits detected. Conclusions: Cytokine armed Lactococcus cremoris AUP-55 enables multimodal action. Treatment with AUP-55 suggests anti-tumor activity as a single therapeutic entity for the treatment of ovarian cancer and peritoneal carcinomatosis.
Long term disease-free survival in locoregional, metastatic and/or recurrent UCNT.
Authors: Imène Hadji
Journal: Journal of Clinical Oncology (2023)

e18023 Background: Undifferentiated Carcinoma of Nasopharyngeal Type (UCNT) is a rare and aggressive type of head and neck cancer related to the Epstein Barr virus (EBV), genetic (HLA B5 in Algeria) and environmental factors. It is the most frequent histological variant of ENT cancers. It has geographically selective epidemiologic features unrelated to external carcinogens, and is known to be radiosensitive and chemosensitive. Methods: Seventy-one patients with biopsy-proven UCNT presenting to a single oncology unit between 2015 and 2022 were assessed for their long-term response to treatment. The sex ratio of cases was 3M: 1F; thirty-one patients (43%) were under the age of 50; 11 (15%) under the age of 35; and among these, there were two 19 year old males. The initial median World Health Organization (WHO) performance status was 1.6. These patients with locoregional (LR), recurrent (REC) and/or metastatic (MTS) UCNT were treated with monthly cycles of platinum-based chemotherapy of cisplatin (CDDP) 75 mg/m 2 IV or Carboplatine AUC-4 and Docetaxel 75 mg/m 2 IV followed by fluorouracil (5FU) 1000 mg/m 2 /day continuous IV infusion days 1 to 4 (TPF) in locally advanced disease, and with cisplatin (CDDP) 75 mg/m 2 day 1 or Carboplatine AUC-5; and fluorouracil (5FU) 1000 mg/m 2 /d continuous IV infusion days 1 to 4 (PF) in recurrent and/or metastatic cases. The choice of systemic therapy was individualized based on patient characteristics including performance status, goals of therapy. Results: Those LR or MTS patients who were still alive without evidence of disease after 36+ months were categorized as complete responders (CRs). A subgroup of CRs was identified who had failed prior chemotherapy. MTS patients with less than three distant osseous sites underwent additional radiation therapy. Conclusions: Encouraging results for this particular type of head and neck cancer confirm the chemosensitivity of UCNT, and the observation of long-term responders makes curability a real consideration.
Practice efficiency of treatment with epcoritamab versus glofitamab in relapsed/refractory diffuse large B-cell lymphoma.
Authors: Kellie Meyer, Danmeng Huang, Ken O'Day, Betsy J. Lahue, Anthony Wang, Alex Mutebi, Samantha Brodkin, Monika P. Jun
Journal: Journal of Clinical Oncology (2023)

e18919 Background: Bispecific antibodies are an emerging class of immunotherapies with demonstrated efficacy in the treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Since epcoritamab is administered subcutaneously, it provides an opportunity for reduced healthcare provider (HCP) and patient burden compared to intravenous (IV) glofitamab. This study assessed HCP and chair time saved treating R/R DLBCL patients with epcoritamab versus glofitamab. Methods: An efficiency model was developed to comprehensively capture time and resources utilized in the administration of epcoritamab and glofitamab from the perspective of institutional decision makers in the United States. The model was informed by the administration process and dosing schedules outlined in the pivotal publications as well as published literature examining HCP’s tasks and the time required to complete these tasks. A 6-month time horizon as was adopted as the base case due to its relevance in the Enhancing Oncology Model, and scenario analyses were performed examining various time horizons. Results: Treating patients with SC epcoritamab compared to IV glofitamab was estimated to reduce HCP time by 29% (45.4 hours for 19 doses of epcoritamab vs. 63.9 hours for 10 doses of glofitamab) and chair time by 38% (55.8 vs. 90.6 hours) per patient over a 6-month time horizon. Time saved for epcoritamab was mainly driven by glofitamab’s infusion time and required pre-treatment with obinutuzumab. For 100 hypothetical patients treated with SC epcoritamab vs. IV glofitamab, a savings of 3,478 chair hours was generated, which could free up capacity to treat 62 additional patients. In the scenario analyses examining different time horizons, the capacity savings advantage of epcoritamab over glofitamab remained. Conclusions: In this model, the use of SC epcoritamab improved practice efficiency compared to IV glofitamab. For institutional decision makers, reduced chair time may increase the total number of treated patients and lead to reduced waiting lists.
Real-world outcomes of patients (pts) with malignant solid tumors treated with immune checkpoint inhibitors (ICI) in relation to smoking status: The SAKK 80/19 SMOKER study.
Authors: Tämer El Saadany, Ulf Petrausch, Alfonso Rojas Mora, Thomas Winder, Christoph Renner, Magdalena Benda, Patrick Reimann, Patrizia Froesch, Andreas Jakob, Adriana Clavijo Daza, Gisela Müller, Roger Anton Fredy Von Moos, Michael Thomas Mark
Journal: Journal of Clinical Oncology (2023)

6619 Background: ICIs are the standard of care for the treatment of different advanced solid organ tumors. Especially in advanced non-small-cell lung cancer, never-smokers were shown to have an inferior outcome when compared to ex-smokers/smokers, suggesting that the smoking status could be a predictive marker for survival benefits under ICI treatment. Methods: Pts within the Swiss Alpine Tumor Immunology Registry (AlpineTIR) treated with an ICI were differentiated by their smoking status (ex-smokers/smokers versus never-smokers). Overall survival (OS) and progression-free survival (PFS) from the start of the first ICI treatment were analyzed by smoking status. Further, subgroup analyses for OS and PFS were done for the most common disease entities. Results: A total of 702 pts were included, from which 455 pts (65%) were ex-smokers/smokers, 213 pts (30%) were never smokers, and 34 pts (5%) had an unknown smoking status. The median follow-up time from the administration of the first ICI to the statistical analysis was 2.7 years (95% CI: 2.3 to 3.2 years). The most frequent tumors were lung cancer (50%), melanoma (13%), renal cell cancer (7%), bladder cancer (6%), and others (24%). Across all indications, the median OS was 1.7 years (95% CI: 1.4 to 2.6 years) for never-smokers (n = 213) and 1.5 years (95% CI: 1.2 to 1.8 years) for smokers (n = 455) (HR: 1.10, 95% CI: 0.89 - 1.37). The median PFS was 6.3 months (95% CI: 4.4 to 8.3 months) for non-smokers and 6.2 months (95% CI: 5.2 to 7.0 months) for smokers (HR: 1.05, 95% CI: 0.87 - 1.27). In lung cancer pts, the median OS was 1.4 years (95% CI: 0.8 to 2.8 years) for never-smokers (n = 43) and 1.4 years (95% CI: 1.2 to 1.7 years) for smokers (n = 302) (HR: 1.02, 95% CI: 0.68 - 1.51). In melanoma pts, the median OS was 3.4 years (95% CI: 1.8 to not reached (NR) years) for never-smokers (n = 54) and 1.7 years (95% CI: 0.8 to NR years) for smokers (n = 34) (HR: 1.35, 95% CI: 0.72 - 2.53). In renal cell cancer pts, the median OS was 1.5 years (95% CI: 1.0 to 3.6 years) for never-smokers (n = 28) and 3.5 years (95% CI: 0.6 to NR years) for smokers (n= 17) (HR: 0.74, 95% CI: 0.31 - 1.78). In bladder cancer pts, the median OS was 1.8 years (95% CI: 0.6 to NR years) for never-smokers (n = 17) and 1.4 years (95% CI: 0.5 to NR years) for smokers (n = 26) (HR: 0.88, 95% CI: 0.39 - 1.99). Conclusions: No survival difference between smokers and non-smokers with metastatic solid organ tumors treated with ICIs could be detected. Interestingly, even in the subgroup of lung cancer pts, no difference was seen. Based on these data, the smoking status should not guide ICI treatment decisions.